One in six coronavirus patients dies after use of hydroxychloroquine, some develop acute heart issues: Study
A research team led by investigators from Brigham and Women's Hospital, US, analyzed real-world evidence related to outcomes for Covid-19 patients
Hospitalized Covid-19 patients, treated with hydroxychloroquine and chloroquine, are more likely to die or develop dangerous heart rhythm complications, according to a large observational study spanning across six continents.
A research team led by investigators from Brigham and Women's Hospital, US, analyzed real-world evidence related to outcomes for Covid-19 patients who were treated with hydroxychloroquine or chloroquine, taken with or without the antibiotics azithromycin or clarithromycin. Investigators did not find any benefit of using hydroxychloroquine or chloroquine, either alone or with antibiotics, on in-hospital outcomes, when initiated early after diagnosis of Covid-19. They found no evidence that either drug regimen reduced the death rate among Covid-19 patients.
“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with Covid-19. No matter which way you examine the data, the use of these drug regimens did not help. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and an increased risk of death. We saw a quadrupling in the rate of significant ventricular arrhythmias in patients with Covid-19 who had been treated with hydroxychloroquine or chloroquine regimens,” says lead author Dr Mandeep R Mehra, executive director of the Brigham and Women's Hospital Center for Advanced Heart Disease in Boston, in the analysis published in The Lancet.
In the study, researchers analyzed data from 96,032 patients hospitalized between December 20, 2019, and April 14, 2020, with laboratory-confirmed SARS-CoV-2 (the virus that causes Covid-19) infection from 671 hospitals, located in North America, Europe, Asia, Africa, South America, and Australia. The study's primary endpoint was death or discharge from the hospital: All of the patients included in the study had either been discharged or had died by April 21.
The research team examined data from nearly 14,888 patients with Covid-19 receiving a combination of any of the four-drug regimens and 81,000 controls. They compared outcomes from patients treated with chloroquine alone (1,868), hydroxychloroquine alone (3,016), chloroquine in combination with an antibiotic (3,783), or hydroxychloroquine with an antibiotic (6,221). Patients from these four groups were compared with the remaining control group of 81,144 patients. All four of the treatments were associated with a higher risk of dying in the hospital.
The analysis shows that 10,698 patients taking one of these drug regimens died in the hospital (11.1%) and 85,334 survived to discharge. The team compared this death rate to that of a control group, after accounting for confounding variables, such as age, sex, and underlying risk factors. The death rate among the control group was 9.3%.
Each of the drug regimens of chloroquine or hydroxychloroquine alone, or in combination with an antibiotic, was associated with an increased risk of in-hospital death with Covid-19, says the team. Overall, about 1 in 6 patients treated with chloroquine or hydroxychloroquine alone died in the hospital. About 1 in 5 treated with chloroquine and an antibiotic died and almost 1 in 4 treated with hydroxychloroquine and an antibiotic died. In contrast, about 1 in 11 patients in the control group died in the hospital.
“At the end of the study period, around one in 11 patients in the control group had died in hospital (9.3%, 7,530 out of 81,144). Of those treated with chloroquine or hydroxychloroquine alone, around one in six patients had died (16.4%, 307 out of 1,868 chloroquine and 18.0%, 543 out of 3,016 hydroxychloroquine). When the drugs were used in combination with a macrolide, the death rate rose to more than one in five for chloroquine (22.2%, 839 out of 3,783) and almost one in four for hydroxychloroquine (23.8%, 1,479 out of 6,221),” the findings state.
Patients treated with hydroxychloroquine or chloroquine regimens were also far more likely to experience abnormal, rapid heart rhythms, known as ventricular arrhythmias, than their counterparts who had not received the drugs. Among the treatment groups, between 4% and 8% of patients experienced a new ventricular arrhythmia, compared to 0.3% of patients in the control group. “After accounting for demographic factors and pre-existing conditions, the team calculated that treatment with this combination of drugs is associated with a more than five-fold increase in the risk of developing a serious heart arrhythmia while in hospital,” says the study.
Based on their findings, the research team suggests these treatment regimens should not be used to treat Covid-19 outside of clinical trials until results from randomized clinical trials are available to confirm the safety and efficacy of these medications for Covid-19 patients.
US President Donald Trump has been hyping hydroxychloroquine as a potential therapy against coronavirus which remains to be approved. The US Food and Drug Administration (FDA) has also cautioned against the use of hydroxychloroquine or chloroquine for Covid-19 outside of the hospital setting or a clinical trial due to the risk of heart rhythm problems.
“To decrease the risk of the heart problems that can be life-threatening, we are warning the public that hydroxychloroquine and chloroquine, either alone or combined with azithromycin when used for Covid-19 should be limited to clinical trial settings or for treating certain hospitalized patients under the Emergency Use Authorization (EUA),” says the FDA.